Dosing challenges in respiratory therapies.

The pulmonary route of administration has been commonly used for local lung conditions such as asthma and chronic obstructive pulmonary disease (COPD). Recently, with the advent of new technologies available for both formulation and device design, molecules usually delivered at high doses, such as antibiotics and insulin to treat cystic fibrosis (CF) and diabetes, respectively, can now be delivered by inhalation as a dry powder. These molecules are generally delivered in milligrams instead of traditional microgram quantities. High dose delivery is most commonly achieved via dry powder inhalers (DPIs), breath activated devices designed with a formulated powder containing micronized drug with aerodynamic diameters between 1 and 5 µm. The powder formulation may also contain other excipients and/or carrier particles to improve the flowability and aerosol dispersion of the powder. A drawback with high doses is that the formulation contains a great number of fine particles, leading to a greater degree of cohesive forces, producing strongly bound agglomerates. With greater cohesive forces holding fine particles together, higher dispersion forces are needed for efficient de-agglomeration and aerosolisation. This requirement of greater dispersion forces has led to different dry powder formulations and vastly different inhaler designs. The purpose of this review is to evaluate the different formulation types, various DPI devices currently available, and how these affect the aerosolisation process and delivery of high dosed inhalable dry powder formulations to the lungs.